Short-term exposure to nicotine does not alter normal basal or NSAID-induced gut barrier function or transit. 51Cr-EDTA and the respective sugar markers correlate well in in vivo permeability testing in healthy humans. The radioactive test detects more NSAID-induced permeability increase than does the lactulose/mannitol ratio permeability test.
Background:
Smoking modulates inflammatory bowel disease, protecting from ulcerative colitis on the one hand and worsening the course of Crohn’s disease on the other. This influence might occur through changes in intestinal permeability, because permeability is increased in most patients with Crohn’s disease.
Aim:
To study the influence of smoking on small intestinal permeability and its increase induced by indomethacin.
Methods:
50 smokers and 50 nonsmokers underwent a 51Cr‐EDTA basal permeability test and the same test after challenge with indomethacin 125 mg p.o.
Results:
Small intestinal permeability was the same in smokers (median 1.22%; IQR 1.00–1.58) and nonsmokers (1.24%; 0.94–1.66). Basal small intestinal permeability was lower in females (1.09%; 0.87–1.33) than in males (1.48%; 1.18–1.88). Indomethacin challenge increased permeability by 110% (71–141) in smokers, vs. 156% (78–220) in the nonsmokers (P=0.04).
Conclusion:
Smoking reduces the effect of NSAID on small intestinal permeability. It is therefore unlikely that the adverse effect of smoking on Crohn’s disease is related to its influence on intestinal permeability.
An evaporative light scattering detector (ELSD) coupled with HPLC was used for the first time to characterize membranes. Polydispersed PEG-200, 600, and 1000 were selected as probe molecules to study the dependence of membrane retention on molecular weight via a gradient eluted HPLC separation coupled to ELSD detection. The results show that HPLC/ELSD is a really general and powerful technique to study the nanofiltration (NF) process since it does not require any special properties for the solutes (chromospheres or fluorophores) and possesses the required sensitivity. Especially in solvent resistant NF (SRNF), where a wide range of organic solvents is used, the ELSD detector was not affected by the interaction between solvent and solutes, which is a critical issue compared to other more common detectors.
We study the effect of three types of mesoporous silica (MPS) particles on the flow of three common excipients: microcrystalline cellulose, lactose and maize starch. While MPS are commonly considered as excipient and also as drug delivery carrier, the effects of MPS as flow aid additive and as powder stabilizer are investigated. MPS particles, called additive in the present study, are found to decrease powder cohesiveness, in particular for powders having higher water content and higher initial cohesiveness. According to both particle and pore size of MPS particles, the effect can be immediate (for small MPS particles having small pore size) or on the longer term (for larger MPS particles having higher pore size). Moreover, the electrostatic properties of the blends are modified by the presence of MPS. The quantity of electrostatic charge created in the blends during a flow in contact with stainless steel is decreased by the addition of MPS. We show that this decrease is induced by a modification of electric resistivity.
Conversion of liquid and semisolid lipids into free flowing powders is an advantageous technique, as the carriers display high surface area, strong adsorption capacity, ease of processing, and ability to generate lipid loaded free flowing powders which can be converted to solid dosage forms like tablets and capsules. A combination of density, adsorption capacity and desorption is found to be of importance in the selection of the right adsorbent. Adsorbents like magnesium aluminium silicates (MAS), granulated fumed silica (GFS) and mesoporous silica gel (MSG) were characterized by flow property measurements, particle size, scanning electron microscopy (SEM) and pore structure by mercury (Hg) intrusion study. SEM results reveal adsorbent morphology, whereas an intrusion-extrusion study reveal pore size distributions. Tablets and capsules of oil loaded adsorbents were prepared by conventional methods. Oil loaded adsorbents were evaluated for the ability to convert oil into powder, easy of processing into tablets and capsules, and release of the loaded oil (Vitamin E) or active (Glyburide). All adsorbents possess good flow property while MSG has higher density than GFS and MAS. This helps to deliver maximum active per unit volume. A wider pore size distribution of MAS was observed in comparison to MSG and GFS. MAS exhibited poor oil release from powder and its formulations, whereas GFS demonstrated closely similar release to MSG. Maximum 70% oil loaded MSG can be delivered in tablet dosage form and MSG can deliver the highest amount in limited volume capsules due to its high density. Hence, lower density and poor oil release from MAS limit its applications in solid oral drug delivery, while both MSG and GFS proved to be suitable.
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